What is the laboratory workup for peripheral neuropathy?

From the Guidelines

The initial laboratory workup for neuropathy should include serum testing for reversible neuropathy causes, such as HbA1c, vitamin B12, TSH, vitamin B6, folate, serum protein electrophoresis, and immunofixation, as well as consideration of additional testing guided by neuropathy phenotype. When evaluating a patient with neuropathy, it is essential to consider the underlying cause, as approximately 30-40% of neuropathies have potentially modifiable underlying conditions 1. The workup and evaluation should include:

• Serum testing for reversible neuropathy causes: HbA1c, vitamin B12, TSH, vitamin B6, folate, serum protein electrophoresis, and immunofixation
• Additional testing guided by neuropathy phenotype: ANA, ESR, CRP, ANCA, anti–smooth muscle, SSA/SSB, RNP, anti-dsDNA, ganglioside ab, anti-MAG, anti-Hu (ANNA-1 ab), thiamine, Lyme, hepatitis B or C, and HIV
• Consideration of MRI spine with or without contrast, as well as MRI brain if cranial nerve involvement is suspected, and MRI plexus if concern for plexus involvement exists 1
• Electrophysiological testing, such as EMG or NCS, may be necessary to characterize the type and severity of neuropathy, especially if initial testing is unrevealing but clinical suspicion remains high 1. It is crucial to note that the diagnosis and management of neuropathy should be guided by the most recent and highest-quality evidence, and a neurology consultation should be considered to guide neuropathy phenotype determination and workup 1.

From the Research

Laboratory Workup for Neuropathy

The laboratory workup for neuropathy typically involves a combination of blood tests, electrodiagnostic studies, and other investigations to determine the underlying cause of the condition.

• Initial blood tests should include:
  • Complete blood count
  • Comprehensive metabolic profile
  • Measurement of erythrocyte sedimentation rate and fasting blood glucose
  • Vitamin B12 and thyroid-stimulating hormone levels 2, 3, 4
• Specialized tests may be ordered if clinically indicated, such as:
  • Serum protein electrophoresis with immunofixation
  • Specific antibody assays
  • Nerve biopsy 3, 4
• Electrodiagnostic studies, including nerve conduction studies and electromyography, can help in the differentiation of axonal versus demyelinating or mixed neuropathy 2, 3
• Lumbar puncture and cerebrospinal fluid analysis may be helpful in the diagnosis of certain conditions, such as Guillain-Barré syndrome and chronic inflammatory demyelinating neuropathy 2

Selection of Laboratory Tests

The selection of laboratory tests should be based on the individual and family history, clinical presentation, and electrophysiological findings 4.

• Basic screening tests for neuropathies should include a blood cell count, thyroid, renal and liver function tests, blood glucose levels, HbA1c, vitamin-B12, and immunofixation 4
• Other laboratory investigations should be carried out only if a specific phenotype is present or if unexpected changes of the disease course occur 4
• Referral to a neuromuscular center may be recommended if basic laboratory parameters fail to uncover the etiology 4

Limitations of Laboratory Tests

Laboratory tests have limited value as a screening tool in asymptomatic populations 5.

• The positive predictive value for an abnormal test resulting in a new medical diagnosis was found to be low, at 0.356 5
• Most abnormal laboratory tests do not result in a new diagnosis, highlighting the need for judicious use of laboratory testing in the evaluation of neuropathy 5